According to one theory, much of the physiological decline of immune responses or homeostasis, is due to programmed death of lymphocytes resulting from the loss of survival signals. As antigens are eliminated, the clones of lymphocytes that were activated by the antigen are deprived of the essential survival stimuli and die by apoptosis. Survival stimuli for lymphocytes function mainly by inducing the expression of anti-apoptotic proteins.
Examples of animal lectins include the galectins (reviewed in Rabinovich et al., 2002, Trends Immunol. 23:313-320; Rabinovich et al., J Leuk Biol 2002, 71: 741-752) or LGALS1 (lectin, galactoside-binding, soluble Blaser C. et al., Euro. J Immunol, 1998, 28: 2311-2319). The galectins, as a family of galactoside binding proteins have potent immunoregulatory activity (reviewed in Rabinovich et al., J Leuk Biol., 2002, 71: 741-752). In particular, galactin-1 is a negative regulator of T-cell responses, inducing apoptosis of T cells (Perillo, N L et al., Nature, 1995, 378(6558):736-739). Galectin-1 is also secreted by activated T cells thereby acting as a self regulator of T cell activation inhibiting antigen-induced proliferation of T cells (Blaser, C et al, as above).
In work leading up to the present invention, the inventor surprisingly discovered that lactulose significantly improves the efficacy of raising and prolonging an immune response to a selected antigen. Not wishing to be bound by any one particular theory or mode of operation, these surprising results are believed to be based at least in part on the ability of a lectin-interactive agent such as lactulose competing with the glycoprotein receptors on the surface of T cells for binding to lectin, thereby inhibiting lectin-induced glycoprotein receptor clustering on the surface of T cells and preventing or attenuating the inhibition of T cell activation.